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Review
. 2013 Jan 29:346:f324.
doi: 10.1136/bmj.f324.

Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis

Dorothea Nitsch  1 , Morgan Grams, Yingying Sang, Corri Black, Massimo Cirillo, Ognjenka Djurdjev, Kunitoshi Iseki, Simerjot K Jassal, Heejin Kimm, Florian Kronenberg, Cecilia M Oien, Andrew S Levey, Adeera Levin, Mark Woodward, Brenda R Hemmelgarn; Chronic Kidney Disease Prognosis Consortium
Collaborators, Affiliations
Review

Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis

Dorothea Nitsch et al. BMJ. .

Abstract

Objective: To assess for the presence of a sex interaction in the associations of estimated glomerular filtration rate and albuminuria with all-cause mortality, cardiovascular mortality, and end stage renal disease.

Design: Random effects meta-analysis using pooled individual participant data.

Setting: 46 cohorts from Europe, North and South America, Asia, and Australasia.

Participants: 2,051,158 participants (54% women) from general population cohorts (n=1,861,052), high risk cohorts (n=151,494), and chronic kidney disease cohorts (n=38,612). Eligible cohorts (except chronic kidney disease cohorts) had at least 1000 participants, outcomes of either mortality or end stage renal disease of ≥ 50 events, and baseline measurements of estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (mL/min/1.73 m(2)) and urinary albumin-creatinine ratio (mg/g).

Results: Risks of all-cause mortality and cardiovascular mortality were higher in men at all levels of estimated glomerular filtration rate and albumin-creatinine ratio. While higher risk was associated with lower estimated glomerular filtration rate and higher albumin-creatinine ratio in both sexes, the slope of the risk relationship for all-cause mortality and for cardiovascular mortality were steeper in women than in men. Compared with an estimated glomerular filtration rate of 95, the adjusted hazard ratio for all-cause mortality at estimated glomerular filtration rate 45 was 1.32 (95% CI 1.08 to 1.61) in women and 1.22 (1.00 to 1.48) in men (P(interaction)<0.01). Compared with a urinary albumin-creatinine ratio of 5, the adjusted hazard ratio for all-cause mortality at urinary albumin-creatinine ratio 30 was 1.69 (1.54 to 1.84) in women and 1.43 (1.31 to 1.57) in men (P(interaction)<0.01). Conversely, there was no evidence of a sex difference in associations of estimated glomerular filtration rate and urinary albumin-creatinine ratio with end stage renal disease risk.

Conclusions: Both sexes face increased risk of all-cause mortality, cardiovascular mortality, and end stage renal disease with lower estimated glomerular filtration rates and higher albuminuria. These findings were robust across a large global consortium.

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Conflict of interest statement

Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare financial support for the submitted work from the Scottish Chief Scientist office (CB) and CKD-PC/the National Kidney Foundation for data extraction (CB) and travel to research related meetings (ASL, DN); ASL has grants pending with the National Kidney Foundation, and NIH; FK received a research grant for the ARO consortium from Amgen and speaker honoraria from Genzyme; No other relationships or activities that could appear to have influenced the submitted work.

Figures

None
Fig 1 Hazard ratios of all-cause mortality according to estimated glomerular filtration rate (A and B) and urinary albumin-creatinine ratio (C and D) in men versus women in general population cohorts and high cardiovascular risk cohorts. Panels A and C show sex-specific hazard ratios including a main effect for male sex at the reference point. Panels B and D show hazard ratios within each sex, thus visually removing the baseline difference between men and women. Hazard ratios were adjusted for age, sex, race, smoking status, systolic blood pressure, history of cardiovascular disease, diabetes, serum total cholesterol concentration, body mass index, and estimated glomerular filtration rate splines or albuminuria
None
Fig 2 Hazard ratios of all-cause mortality at estimated glomerular filtration rate of 45 (v rate of 95) in women and men per study. Hazard ratios were adjusted for age, sex, race, smoking status, systolic blood pressure, history of cardiovascular disease, diabetes, serum total cholesterol concentration, body mass index, and albuminuria
None
Fig 3 Hazard ratios of all-cause mortality at urinary albumin-creatinine ratio of 30 (v ratio of 5) in women and men per study. Hazard ratios were adjusted for age, sex, race, smoking status, systolic blood pressure, history of cardiovascular disease, diabetes, serum total cholesterol concentration, body mass index, and estimated glomerular filtration rate splines.
None
Fig 4 Hazard ratios of end stage renal disease according to estimated glomerular filtration rate (A and B) and urinary albumin-creatinine ratio (C and D) in men versus women in chronic kidney disease cohorts. Panels A and C show sex-specific hazard ratios including a main effect for male sex at the reference point. Panels B and D show hazard ratios within each sex, thus visually removing the baseline difference between men and women. Hazard ratio were adjusted for age, sex, race, smoking status, systolic blood pressure, history of cardiovascular disease, diabetes, serum total cholesterol concentration, body mass index, and estimated glomerular filtration rate splines or albuminuria
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